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Ali Khamesipour - One of the best experts on this subject based on the ideXlab platform.
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the leishmanicidal effect of lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica
Parasites & Vectors, 2021Co-Authors: Sara Rahimi, Ali Khamesipour, Amir Ahmad Akhavan, Javad Rafinejad, Reza Ahmadkhaniha, Mahmood Bakhtiyari, Arshad Veysi, Kamran AkbarzadehAbstract:Leishmaniasis is a major parasitic disease worldwide, except in Australia and Antarctica, and it poses a significant public health problem. Due to the absence of safe and effective vaccines and drugs, researchers have begun an extensive search for new drugs. The aim of the current study was to investigate the in vitro leishmanicidal activity of larval saliva and hemolymph of Lucilia sericata on Leishmania tropica. The effects of different concentrations of larval products on promastigotes and intracellular amastigotes of L. tropica were investigated using the mouse cell line J774A.1 and peritoneal macrophages as host cells. The 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and direct observation and counting method were used to assess the inhibitory effects and cell cytotoxicity of the larval products. The effects of larval products on the amastigote form of L. tropica were quantitatively estimated by calculating the rate of macrophage infection, number of amastigotes per infected macrophage cell, parasite load and survival index. The 50% cytotoxicity concentration (CC50) value of both larval saliva and hemolymph was 750 µg/ml, and the 50% inhibitory concentration (IC50) values were 134 µg/ml and 60 µg/ml for larval saliva and larval hemolymph, respectively. The IC50 for Glucantime, used a positive control, was (11.65 µg/ml). Statistically significant differences in viability percentages of promastigotes were observed for different doses of both larval saliva and hemolymph when compared with the negative control (p ≤ 0.0001). Microscopic evaluation of the amastigote forms revealed that treatment with 150 µg/ml larval hemolymph and 450 µg/ml larval saliva significantly decreased the rate of macrophage infection and the number of amastigotes per infected macrophage cell. Larval saliva and hemolymph of L. sericata have acceptable leishmanicidal properties against L. tropica.
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the leishmanicidal effect of lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica
Parasites & Vectors, 2021Co-Authors: Sara Rahimi, Ali Khamesipour, Amir Ahmad Akhavan, Javad Rafinejad, Reza Ahmadkhaniha, Mahmood Bakhtiyari, Arshad Veysi, Kamran AkbarzadehAbstract:BACKGROUND Leishmaniasis is a major parasitic disease worldwide, except in Australia and Antarctica, and it poses a significant public health problem. Due to the absence of safe and effective vaccines and drugs, researchers have begun an extensive search for new drugs. The aim of the current study was to investigate the in vitro leishmanicidal activity of larval saliva and hemolymph of Lucilia sericata on Leishmania tropica. METHODS The effects of different concentrations of larval products on promastigotes and intracellular amastigotes of L. tropica were investigated using the mouse cell line J774A.1 and peritoneal macrophages as host cells. The 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and direct observation and counting method were used to assess the inhibitory effects and cell cytotoxicity of the larval products. The effects of larval products on the amastigote form of L. tropica were quantitatively estimated by calculating the rate of macrophage infection, number of amastigotes per infected macrophage cell, parasite load and survival index. RESULTS The 50% cytotoxicity concentration (CC50) value of both larval saliva and hemolymph was 750 µg/ml, and the 50% inhibitory concentration (IC50) values were 134 µg/ml and 60 µg/ml for larval saliva and larval hemolymph, respectively. The IC50 for Glucantime, used a positive control, was (11.65 µg/ml). Statistically significant differences in viability percentages of promastigotes were observed for different doses of both larval saliva and hemolymph when compared with the negative control (p ≤ 0.0001). Microscopic evaluation of the amastigote forms revealed that treatment with 150 µg/ml larval hemolymph and 450 µg/ml larval saliva significantly decreased the rate of macrophage infection and the number of amastigotes per infected macrophage cell. CONCLUSION Larval saliva and hemolymph of L. sericata have acceptable leishmanicidal properties against L. tropica.
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identification of antimony resistance markers in Leishmania tropica field isolates through a cdna aflp approach
Experimental Parasitology, 2013Co-Authors: Elham Kazemirad, Homa Hajjaran, Ramtin Hadighi, Mojtaba Saffari, Mohammad Bagher Khademerfan, Reza Raoofian, Ali Khamesipour, Mehdi Mohebali, Sassan RezaieAbstract:Pentavalent antimonial compounds have been the first line therapy for Leishmaniasis; unfortunately the rate of treatment failure of anthroponotic cutaneous Leishmaniasis (ACL) is increasing due to emerging of drug resistance. Elucidation of the molecular mechanisms operating in antimony resistance is critical for development of new strategies for treatment. Here, we used a cDNA-AFLP approach to identify gene(s) which are differentially expressed in resistant and sensitive Leishmania tropica field isolates. We identified five genes, aquaglyceroporin (AQP1) acts in drug uptake, ATP-binding cassette (ABC) transporter (MRPA) involved in sequestration of drug, phosphoglycerate kinase (PGK) implicated in glycolysis metabolism, mitogen activated protein kinase (MAPK) and protein tyrosine phosphatase (PTP) responsible for phosphorylation pathway. The results were confirmed using real time RT-PCR which revealed an upregulation of MRPA, PTP and PGK genes and downregulation of AQP1 and MAPK genes in resistant isolate. To our knowledge, this is the first report of identification of PTP and PGK genes potentially implicated in resistance to antimonials. Our findings support the idea that distinct biomolecules might be involved in antimony resistance in L. tropica field isolates.
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overexpression of ubiquitin and amino acid permease genes in association with antimony resistance in Leishmania tropica field isolates
Korean Journal of Parasitology, 2013Co-Authors: Elham Kazemirad, Homa Hajjaran, Ramtin Hadighi, Mojtaba Saffari, Mohammad Bagher Khademerfan, Sassan Rezaie, Reza Raoofian, Ali Khamesipour, Mehdi Mohebali, Mansour HeidariAbstract:The mainstay therapy against Leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous Leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime®) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance.
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the effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate
Parasitology Research, 2012Co-Authors: Azar Shokri, Ali Khamesipour, Iraj Sharifi, Nozar Nakhaee, Majid Fasihi Harandi, Jafar Nosratabadi, Maryam Hakimi Parizi, Mohammad BaratiAbstract:Pentavalent antimonials are the standard treatment for cutaneous Leishmaniasis (CL) with low efficacy and resistance is emerging. CL is increased significantly in respect to incidence rate and expanding to new foci. In the present study, the effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate (MA, Glucantime) was evaluated using colorimetric assay (MTT) and in a macrophage model, respectively. Verapamil, as a calcium channel blocker, affects drug uptake by preventing of drug efflux from the cells. In promastigote form, several concentrations of MA with or without verapamil showed significant decrease (P < 0.05) in optical density. The overall mean IC50 value with combination of MA plus verapamil (IC50 = 116.03 μg/ml) was significantly less than MA (IC50 = 225.14 μg/ml) alone (P < 0.05) for promastigote stage. Similarly, the amastigote stage was more susceptible to treatment with MA plus verapamil to that of MA alone (P < 0.05). Analysis of overall effect of different concentrations of MA alone, compared with combination of MA plus verapamil by mean infection rate of amastigotes in each macrophage showed a significant difference (P < 0.05).These findings indicated some degree of synergistic effects between MA and verapamil on in vitro susceptibility of L. tropica to MA. Further works are required to evaluate this synergistic effect on animal model or volunteer human subjects.
Ramtin Hadighi - One of the best experts on this subject based on the ideXlab platform.
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comparative mitochondrial proteomics of Leishmania tropica clinical isolates resistant and sensitive to meglumine antimoniate
Parasitology Research, 2020Co-Authors: Minoo Tasbihi, Homa Hajjaran, Faezeh Shekari, Majid Khanmohammadi, Ramtin HadighiAbstract:Antimony is an important drug for the treatment of Leishmania parasite infections. In several countries, the emergence of drug-resistant Leishmania species has reduced the effectiveness of this drug. The mechanism of clinical drug resistance is unclear. The aim of this work was to identify mitochondrial proteome alterations associated with resistance against antimonial. A combination of cell fractionation, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and Label-Free Quantification was used to characterize the mitochondrial protein composition of Leishmania tropica field isolates resistant and sensitive to meglumine antimoniate. LC-MS/MS analysis resulted in the identification of about 1200 proteins of the Leishmania tropica mitochondrial proteome. Various criteria were used to allocate about 40% proteins to mitochondrial proteome. Comparative quantitative proteomic analysis of the sensitive and the resistant strains showed proteins with differential abundance in resistance species are involved in TCA and aerobic respiration enzymes, stress proteins, lipid metabolism enzymes, and translation. These results showed that the mechanism of antimony resistance in Leishmania spp. field isolate may be associated with alteration in enzymes involved in mitochondrial pathways.
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identification of antimony resistance markers in Leishmania tropica field isolates through a cdna aflp approach
Experimental Parasitology, 2013Co-Authors: Elham Kazemirad, Homa Hajjaran, Ramtin Hadighi, Mojtaba Saffari, Mohammad Bagher Khademerfan, Reza Raoofian, Ali Khamesipour, Mehdi Mohebali, Sassan RezaieAbstract:Pentavalent antimonial compounds have been the first line therapy for Leishmaniasis; unfortunately the rate of treatment failure of anthroponotic cutaneous Leishmaniasis (ACL) is increasing due to emerging of drug resistance. Elucidation of the molecular mechanisms operating in antimony resistance is critical for development of new strategies for treatment. Here, we used a cDNA-AFLP approach to identify gene(s) which are differentially expressed in resistant and sensitive Leishmania tropica field isolates. We identified five genes, aquaglyceroporin (AQP1) acts in drug uptake, ATP-binding cassette (ABC) transporter (MRPA) involved in sequestration of drug, phosphoglycerate kinase (PGK) implicated in glycolysis metabolism, mitogen activated protein kinase (MAPK) and protein tyrosine phosphatase (PTP) responsible for phosphorylation pathway. The results were confirmed using real time RT-PCR which revealed an upregulation of MRPA, PTP and PGK genes and downregulation of AQP1 and MAPK genes in resistant isolate. To our knowledge, this is the first report of identification of PTP and PGK genes potentially implicated in resistance to antimonials. Our findings support the idea that distinct biomolecules might be involved in antimony resistance in L. tropica field isolates.
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overexpression of ubiquitin and amino acid permease genes in association with antimony resistance in Leishmania tropica field isolates
Korean Journal of Parasitology, 2013Co-Authors: Elham Kazemirad, Homa Hajjaran, Ramtin Hadighi, Mojtaba Saffari, Mohammad Bagher Khademerfan, Sassan Rezaie, Reza Raoofian, Ali Khamesipour, Mehdi Mohebali, Mansour HeidariAbstract:The mainstay therapy against Leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous Leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime®) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance.
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Comparative proteomics study on meglumine antimoniate sensitive and resistant Leishmania tropica isolated from Iranian anthroponotic cutaneous Leishmaniasis patients.
Eastern Mediterranean Health Journal, 2012Co-Authors: Homa Hajjaran, Bahareh Azarian, Ramtin Hadighi, Ahmadreza Assareh, Mehdi Mohebali, Behrouz VaziriAbstract:: In order to define the protein expressional changes related to the process of meglumine antimoniate resistance in anthroponotic cutaneous Leishmaniasis (CL), we performed a comparative proteomics analysis on sensitive and resistant strains of Leishmania tropica isolated from Iranian CL patients. Cell proteins were analysed with 2-dimensional electrophoresis and differentially expressed proteins were identified by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor(LACK), alpha tubulin (x2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. The study shows the usefulness of proteomics in identifying proteins that may express differences between sensitive and resistant L. tropica isolates.
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glucantime resistant Leishmania tropica isolated from iranian patients with cutaneous Leishmaniasis are sensitive to alternative antiLeishmania drugs
Parasitology Research, 2007Co-Authors: Ramtin Hadighi, Ali Khamesipour, Patrick Boucher, Ahmad Reza Meamar, G Roy, Marc Ouellette, Mehdi MohebaliAbstract:Cutaneous Leishmaniasis (CL) is a major health problem in endemic areas of Iran. The pentavalent antimony (SbV) based drug Glucantime is the first line of treatment for CL in Iran, but recently SbV-resistant Leishmania tropica isolates derived from unresponsive patients were reported. We show in this study that these resistant parasites are cross-resistant to the other SbV-containing drug Pentostam and at least for one isolate also to amphotericin B. However, these resistant isolates were shown to be sensitive to miltefosine and paromomycin. The latter two drugs could thus be useful alternatives for the treatment of Leishmaniasis in Iran even for SbV-resistant isolates.
Milena Svobodová - One of the best experts on this subject based on the ideXlab platform.
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Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse
2013Co-Authors: Yahya Sohrabi, Helena Havelková, Tetyana Kobets, Matyáš Šíma, Valeriya Volkova, Igor Grekov, Taťána Jarošíková, Iryna Kurey, Jarmila Vojtíšková, Milena SvobodováAbstract:BackgroundL. tropica can cause both cutaneous and visceral Leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the recombinant congenic strain CcS-16 carrying 12.5% genes from the resistant parental strain STS/A and 87.5% genes from the susceptible strain BALB/c is more susceptible to L. tropica than BALB/c. We used these strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.MethodsWe analyzed genetics of response to L. tropica in infected F2 hybrids between BALB/c×CcS-16. CcS-16 strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice and tested their linkage with pathological changes and systemic immune responses.Principal FindingsWe mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loci affect different subsets of responses, exhibit organ specific effects and a separate control of parasite load and organ pathology.ConclusionWe present the first identification of genetic loci controlling susceptibility to L. tropica. The different combinations of alleles controlling various symptoms of the disease likely co-determine different manifestations of disease induced by the same pathogen in individual mice.
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genetics of host response to Leishmania tropica in mice different control of skin pathology chemokine reaction and invasion into spleen and liver
PLOS Neglected Tropical Diseases, 2012Co-Authors: Tetyana Kobets, Milena Svobodová, Yahya Sohrabi, Helena Havelková, Valeriya Volkova, Igor Grekov, Iryna Kurey, Jarmila Vojtíšková, Martina Slapnickova, Peter DemantAbstract:Background Leishmaniasis is a disease caused by protozoan parasites of genus Leishmania. The frequent involvement of Leishmania tropica in human Leishmaniasis has been recognized only recently. Similarly as L. major, L. tropica causes cutaneous Leishmaniasis in humans, but can also visceralize and cause systemic illness. The relationship between the host genotype and disease manifestations is poorly understood because there were no suitable animal models.
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Leishmania tropica in rock hyraxes procavia capensis in a focus of human cutaneous Leishmaniasis
American Journal of Tropical Medicine and Hygiene, 2010Co-Authors: Dalit Talmifrank, Roni King, Charles L. Jaffe, Milena Svobodová, Alon Warburg, Abedelmajeed Nasereddin, Ofer Peleg, Gad BanethAbstract:Cutaneous Leishmaniasis, caused by Leishmania tropica, has recently emerged in urban and rural foci of central and northern Israel, and constitutes a major public health concern. Rock hyraxes (Procavia capensis), the suspected natural reservoir, were trapped in the cutaneous Leishmaniasis urban focus of Maale Adumim in central Israel and evaluated for L. tropica infection by real-time kinetoplast DNA (kDNA) polymerase chain reaction (PCR) and serology. Real-time PCR on blood and computerized western blot serology analysis was positive for L. tropica in 58% and 80%, respectively, of the hyraxes tested. Phylogenetic analysis of the ribosomal internal transcribed spacer 1 region indicated that similar genotypes were present in humans and hyraxes from the same habitat. The high rates of infection and exposure to L. tropica among hyraxes supports their involvement in the transmission cycle of this parasite, and their potential role as a reservoir for human disease.
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distinct transmission cycles of Leishmania tropica in 2 adjacent foci northern israel
Emerging Infectious Diseases, 2006Co-Authors: Milena Svobodová, Jan Votýpka, Gad Baneth, Jitka Peckova, Vit Dvorak, Abedelmajeed Nasereddin, Julia Sztern, Vasiliy D Kravchenko, Amnon Orr, David MeirAbstract:Transmission of Leishmania tropica was studied in 2 adjacent foci in Israel where vector populations differ. Only Phlebotomus sergenti was found infected with L. tropica in the southern focus; P. arabicus was the main vector in the northern focus. Rock hyraxes (Procavia capensis) were incriminated as reservoir hosts in both foci. L. tropica strains from the northern focus isolated from sand flies, cutaneous Leishmaniasis cases, and rock hyraxes were antigenically similar to L. major, and strains from the southern focus were typically L. tropica. Laboratory studies showed that P. arabicus is a competent vector of L. tropica, and P. sergenti is essentially refractory to L. tropica from the northern focus. Susceptibility of P. arabicus may be mediated by O glycoproteins on the luminal surface of its midgut. The 2 foci differ with respect to parasites and vectors, but increasing peridomestic rock hyrax populations are probably responsible for emergence of cutaneous Leishmaniasis in both foci.
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Experimental transmission of Leishmania tropica to hyraxes (Procavia capensis) by the bite of Phlebotomus arabicus.
Microbes and infection, 2006Co-Authors: Milena Svobodová, Petr Volf, Jan VotýpkaAbstract:The ability of the sand fly Phlebotomus (Adlerius) arabicus to transmit Leishmania tropica was studied experimentally using hyraxes (Procavia capensis), natural reservoir hosts of the parasite. Sand flies became infected with L. tropica after feeding on a lesion of needle-inoculated hyrax. Moreover, P. arabicus fed with L. tropica promastigotes transmitted the parasite to hyraxes by bite during a second bloodmeal. Although the animals remained asymptomatic after infective sand fly bite, they were PCR positive and infectious for naive sand flies. We have thus demonstrated cyclical transmission of L. tropica by P. arabicus in hyraxes. This confirms experimentally the vectorial competence of P. (Adlerius) arabicus, and demonstrates that asymptomatic reservoir hosts are infectious to appropriate vectors.
F Pratlong - One of the best experts on this subject based on the ideXlab platform.
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microsatellite analysis reveals genetic structure of Leishmania tropica
International Journal for Parasitology, 2006Co-Authors: Jan M. Schwenkenbecher, Charles L. Jaffe, F Pratlong, Amer Aljawabreh, Thierry Wirth, L F Schnur, Henk D F H Schallig, Omar Hamarsheh, Kifaya Azmi, Gabriele SchönianAbstract:The current rapid spread of Leishmaniases caused by Leishmania tropica and the complexity of its clinical spectrum call for this parasite's epidemiological and evolutionary investigation. Evaluation of its population structure by isoenzyme electrophoresis and previous molecular biological analysis has proved difficult. In this study, we used 21 microsatellite loci to type 117 strains from different African and Asian locations. Eighty-one different genotypes were found. A genetic bottleneck supported by a gradient in the number of alleles and consistent with the geographical structure of the Middle East suggests an African origin of this species. A Bayesian approach identified 10 genetic clusters that correlated predominantly with geographical origin. The strains in the 'Asia' cluster form a very heterogeneous sub-population, with a varied but inter-related genotype that is geographically very widely dispersed and consistent with anthroponotic transmission of the parasite. The other nine clusters were more homogenous. The propagation of L. tropica appears to be predominantly clonal. In Africa and the Middle East, anthroponotic and zoonotic systems of distribution may contribute to the development of overlapping, genetically distinct populations of L. tropica.
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Leishmaniasis due to Leishmania tropica mon 102 in a new moroccan focus
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2004Co-Authors: M Rhajaoui, F Pratlong, H Fellah, J P Dedet, M LyagoubiAbstract:In Morocco, between March and April 2002, large numbers of human leihsmaniasis cases were detected during a survey at Zouagha My Yacoub province in Fes State. Among 95 cases, 76 were positive by direct observation of Giemsa-stained smears. Sixteen stocks were isolated in NNN medium and identified as Leishmania tropica MON-102, using isoenzyme techniques on starch gel electrophoresis.
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a new Leishmania tropica zymodeme causative agent of canine visceral Leishmaniasis in northern morocco
Annals of Tropical Medicine and Parasitology, 2002Co-Authors: M Lemrani, R Nejjar, F PratlongAbstract:(2002). A new Leishmania tropica zymodeme—causative agent of canine visceral Leishmaniasis in northern Morocco. Annals of tropical Medicine & Parasitology: Vol. 96, No. 6, pp. 637-638.
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Leishmania tropica au maroc iii role vecteur de phlebotomus sergenti a propos de 89 isolats
Annales de parasitologie humaine et comparée, 1991Co-Authors: E Guilvard, J. A. Rioux, Montserrat Gallego, F Pratlong, J Mahjour, E Martinezortega, J Dereure, A Saddiki, A MartiniAbstract:A l’occasion de l’analyse ecoepidemiologique d’un mesofoyer marocain de leishmaniose cutanee a Leishmania tropica, 7 907 Phlebotomes ♀, captures au piege CDC, ont ete disseques, de l’ete a l’automne 1989. Parmi les especes du genre Phlebotomus, seul P. sergenti etait porteur de promastigotes. Quatre-vingt-neuf souches, appartenant au complexe L. tropica , ont ete ainsi isolees. La frequence de l’infestation vectorielle, nulle en juin, est passee a 1,3 % en aout, pour atteindre 9,9 % en octobre, situant la periode a risque en fin de saison chaude. Sur les 89 souches isolees, 74, entierement typees, ont ete rapportees aux quatre zymodemes suivants : MON-102 (1 souche), MON-107 (56 souches), MON-122 (2 souches) et MON-123 (15 souches). Seuls les deux premiers ont ete observes chez l’Homme. La repartition des zymodemes MON-102 et MON-107 etait tres differente chez l’Homme, le Chien et le vecteur : dans l'un des sites prospectes ou dominait largement MON-107, l’absence de cas humains dus a ce zymodeme evoque l’existence d’un reservoir sauvage.
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Leishmania tropica au maroc iv diversite isozymique intrafocale
Annales de parasitologie humaine et comparée, 1991Co-Authors: F Pratlong, J. A. Rioux, E Guilvard, Montserrat Gallego, J Mahjour, J Dereure, A Martini, G Lanotte, J Perieres, A SaddikiAbstract:L’analyse ecoepidemiologique d’un foyer marocain de leishmaniose cutanee a Leishmania tropica a permis d’observer un important polymorphisme enzymatique. Sept zymodemes, appartenant a ce complexe, ont ete identifies sur la base de 149 souches, isolees de l’Homme, du Chien et du vecteur Phlebotomus sergenti. Les parasites se repartissent en trois sous-groupes dont deux composes de trois zymodemes « petits variants ». Cette diversite parait en rapport avec l’anciennete de l’infestation qui aurait permis la colonisation d’un meme foyer par des zymodemes d’origines geographiques differentes. La diversification en « petits variants » serait due a des mutations recentes, eventuellement assorties d’echanges genetiques.
Mehdi Mohebali - One of the best experts on this subject based on the ideXlab platform.
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Leishmania tropica in stray dogs in southeast iran
Iranian Journal of Public Health, 2015Co-Authors: Mehdi Bamorovat, Mehdi Mohebali, Iraj Sharifi, Majid Fasihi Harandi, Shahriar Dabiri, Mohammad Ali Mohammadi, Mohammad Reza Aflatoonian, Alireza KeyhaniAbstract:Background: Cutaneous Leishmaniasis (CL) caused by Leishmania tropica is endemic in Kerman, southeastern Iran. While dogs have long been implicated as the main domestic reservoirs of L. infantum, etiological agent of zoonotic visceral Leishmaniasis (ZVL), they can also carry L. tropica infection. The objective of the present study was to determine molecular identity and to evaluate histopathological changes due to CL in dogs in a well-known focus of anthroponotic CL (ACL) in Kerman, southeastern Iran. Methods: This study was carried out in three prospective series from 1994 to 2013 on dogs. Tissue samples were taken from 471 stray dogs. Pathological specimens including skin, spleen, liver and lymph nodes were prepared for paraffin blocks, sectioning and staining for further histopathological examination. PCR amplification of kDNA was performed to identify the causative agent and sequencing. Overall, two out of 471 stray dogs were infected with L. tropica. Hyperplasia of red pulp by the proliferation of histiocytes, lymphocytes, plasma cells and cytoplasm of histiocytes collection of amastigotes was noted. Results: Based on the results of PCR products and sequencing analysis, the parasites isolated from the lesions of two dogs were characterized as L. tropica, corresponding to a band of 830 bp Conclusion: This finding revealed infection with L. tropica in stray dogs in the city and suburbs of Kerman. This information is essential for public health concerns and planning effective future control programs. The role of dogs as potentional reservoir in the epidemiology of ACL needs further investigation.
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identification of antimony resistance markers in Leishmania tropica field isolates through a cdna aflp approach
Experimental Parasitology, 2013Co-Authors: Elham Kazemirad, Homa Hajjaran, Ramtin Hadighi, Mojtaba Saffari, Mohammad Bagher Khademerfan, Reza Raoofian, Ali Khamesipour, Mehdi Mohebali, Sassan RezaieAbstract:Pentavalent antimonial compounds have been the first line therapy for Leishmaniasis; unfortunately the rate of treatment failure of anthroponotic cutaneous Leishmaniasis (ACL) is increasing due to emerging of drug resistance. Elucidation of the molecular mechanisms operating in antimony resistance is critical for development of new strategies for treatment. Here, we used a cDNA-AFLP approach to identify gene(s) which are differentially expressed in resistant and sensitive Leishmania tropica field isolates. We identified five genes, aquaglyceroporin (AQP1) acts in drug uptake, ATP-binding cassette (ABC) transporter (MRPA) involved in sequestration of drug, phosphoglycerate kinase (PGK) implicated in glycolysis metabolism, mitogen activated protein kinase (MAPK) and protein tyrosine phosphatase (PTP) responsible for phosphorylation pathway. The results were confirmed using real time RT-PCR which revealed an upregulation of MRPA, PTP and PGK genes and downregulation of AQP1 and MAPK genes in resistant isolate. To our knowledge, this is the first report of identification of PTP and PGK genes potentially implicated in resistance to antimonials. Our findings support the idea that distinct biomolecules might be involved in antimony resistance in L. tropica field isolates.
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overexpression of ubiquitin and amino acid permease genes in association with antimony resistance in Leishmania tropica field isolates
Korean Journal of Parasitology, 2013Co-Authors: Elham Kazemirad, Homa Hajjaran, Ramtin Hadighi, Mojtaba Saffari, Mohammad Bagher Khademerfan, Sassan Rezaie, Reza Raoofian, Ali Khamesipour, Mehdi Mohebali, Mansour HeidariAbstract:The mainstay therapy against Leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous Leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime®) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance.
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Comparative proteomics study on meglumine antimoniate sensitive and resistant Leishmania tropica isolated from Iranian anthroponotic cutaneous Leishmaniasis patients.
Eastern Mediterranean Health Journal, 2012Co-Authors: Homa Hajjaran, Bahareh Azarian, Ramtin Hadighi, Ahmadreza Assareh, Mehdi Mohebali, Behrouz VaziriAbstract:: In order to define the protein expressional changes related to the process of meglumine antimoniate resistance in anthroponotic cutaneous Leishmaniasis (CL), we performed a comparative proteomics analysis on sensitive and resistant strains of Leishmania tropica isolated from Iranian CL patients. Cell proteins were analysed with 2-dimensional electrophoresis and differentially expressed proteins were identified by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor(LACK), alpha tubulin (x2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. The study shows the usefulness of proteomics in identifying proteins that may express differences between sensitive and resistant L. tropica isolates.
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disseminated Leishmaniasis caused by Leishmania tropica in hiv positive patients in the islamic republic of iran
Eastern Mediterranean Health Journal, 2010Co-Authors: S Jafari, Homa Hajjaran, Mehdi Mohebali, M Hajiabdolbaghi, Hesam HashemianAbstract:Both cutaneous and visceral forms of Leishmaniasis are prevalent in some parts of the Islamic Republic of Iran [1,2]. The Mediterranean type of visceral Leishmaniasis (VL) is also reported sporadically throughout the country [3] with canines being the main animal reservoir hosts [4]. The cutaneous form of Leishmaniasis is seen in 2 forms: anthroponotic and zoonotic. Anthroponotic cutaneous Leishmaniasis (ACL) is caused by Leishmania tropica and is prevalent in many largeand medium-sized cities in the country [1,5]. Zoonotic cutaneous Leishmaniasis (ZCL) is caused by L. major and is endemic in many foci in the north, east and south of the country [6]. Some studies have implicated L. tropica as another agent of VL in humans and dogs in reports from the north-west and south of the country [4,7,8]. Few data are available, however, about host immunological response and parasite destruction when Leishmaniasis is associated with immunosuppressants. At present, the majority of cases of HIV– Leishmaniasis co-infection reported in the Mediterranean basin were caused by L. infantum [9]. Disseminated Leishmaniasis caused by L. tropica in patients with HIV infection is uncommon. Here, we report on 2 patients with HIV–Leishmaniasis co-infection caused by L. tropica with generalized and multiple skin lesions and visceral involvement. This is the first such report from the Islamic Republic of Iran.